Rabies is a major zoonotic disease that remains an important public health problem, causing 60,000 annual deaths worldwide. In most developing countries, dogs represent the major rabies reservoir, whereas the situation in the Americas is much more complex, since large reservoirs of rabies viruses exist in many wild animal species. In the US, wildlife reservoirs accounted for nearly 93% of the 8,513 reported cases of rabies in 1997. The most frequently reported rabid wildlife species is raccoon (50.5%), followed by skunk (24.0%). Outbreaks of rabies infection in these terrestrial mammals are found in broad geographic areas across the US. For example, raccoon rabies affects an area of more than 1 million square kilometers from Florida to Maine.
Oral immunization of wildlife with live vaccines, such as the modified-live rabies virus vaccines SAD B19, SAG-1, and SAG-2 or the vaccinia-rabies glycoprotein recombinant virus vaccine VRG, is the most effective method to control and eventually eradicate rabies. In the past decade, more than 15 million baits containing VRG have been distributed in the US through programs designed to control rabies among free-ranging raccoons, foxes and coyotes. Since 1997, oral vaccination campaigns in Ohio have led to a highly significant reduction in raccoon rabies without any adverse effects in humans. However, in September 2000, a person who was exposed to VRG during an oral vaccination campaign developed severe local inflammatory reactions. This incident underlines the heightened need for safer live rabies vaccines, particularly as wildlife rabies vaccination efforts in the US intensify on a national level.